Helicobacter pylori is a human gastric pathogen which is extremely well adapted to the low pH environment of the stomach, since it has evolved mechanisms to survive both severe acid shocks and to grow under mildly acidic conditions. Central to the acid resistance of H. pylori is the enzyme urease whose function is to maintain the cytoplasmic and periplasmic pH of the bacterium near neutrality. Substantial progress has been made recently in unravelling the complex regulation of urease expression and the expression of additional genes involved in the acid adaptation of H. pylori. Acid-responsive gene regulation involves the two-component system ArsRS and the metal responsive pleiotropic transcriptional regulators NikR and Fur which control partially overlapping regulons. Here we review our current understanding of the mechanisms of transcriptional regulation governing the acid response of H. pylori.